Burn Wound Progression Research Articles

Are Breast Implants Anticarcinogenic? A 14-Year Follow-Up of the Los Angeles Study

Endothelins are well-known vasoconstrictor peptides produced by vascular endothelial cells that have been reported to have a fundamental role in regulation of the systemic blood circulation. Plasma levels of endothelins are increased by burn injury, which also causes thrombosis and occlusion of vessels in the dermis as well as a vascular response in the adjacent uninjured dermis. Diminished blood flow leads to progressive ischemia and necrosis of the dermis beneath and around the burn (zone of stasis). If blood flow could be restored in this zone, secondary tissue damage would be minimized. In this study we examined the effects of a new nonselective endothelin receptor antagonist, TAK-044 (Takeda Chemical Industries, Ltd., Osaka, Japan), on burn trauma in rats. Fifty male Sprague-Dawley rats weighing an average of 450 gm were burned with a brass probe that produced a row of three burns 10 x 30 mm in size and two intervening unburned areas 5 x 30 mm in size. Rats were divided into five groups of 10 animals. Four groups received 0.01, 0.1, 1 or 10 mg/kg of TAK-044 via the dorsal vein of the penis immediately after burn trauma, while the control group received the same volume of saline. Skin blood flow was measured with a laser-Doppler flowmeter, and the development of edema and the area of necrotic tissue also were determined. Inhibition of endothelin activity by TAK-044 after burn injury improved microvascular perfusion in the zone of stasis and prevented the progression of tissue damage in this zone. This supports the role of endothelins in the progression of burn injury in the zone of stasis. TAK-044 was most effective in preventing progressive burn damage at a dose of 1 mg/kg. The extent of necrosis and edema was reduced significantly, and blood flow in the zone of stasis was increased in the treated rats.

Inhibition of leukocyte-endothelial adherence following thermal injury

Progressive microvascular damage in the tissue adjacent to a cutaneous burn injury results in extension of burn size. The role of neutrophils (PMNs) in the pathogenesis of microvascular injury was investigated by inhibition of PMN adherence to the microvascular endothelium using monoclonal antibodies directed to the leukocyte CD18 adhesion complex or its endothelial ligand, intercellular adhesion molecule-1 (ICAM-1, CD54). A model of thermal injury was developed using New Zealand White rabbits. Under general anesthesia two sets of three full-thickness burns separated by two 5 × 30-mm zones were produced by applying brass probes heated to 100°C to the animals' backs for 30 sec. Cutaneous blood flow determinations were obtained for 72 hr. Blood flow measurements were performed using a laser doppler blood flowmeter (PF3, Perimed, Piscataway, NJ). There were five experimental groups; controls given saline alone, n = 12; animals given monoclonal antibody to the PMN CD18 complex, R 15.7 prior to burn injury (pre-R15.7, n = 5); animals given R 15.7 30 min after burn injury (post-R 15.7, n = 6); animals given the anti ICAM-1 antibody, R 6.5 prior to burn (pre-R 6.5, n = 6); and animals given the R 6.5 30 min postburn injury (post-R 6.5, n = 6). BF in the marginal “zone of stasis” between burn contact sites was significantly higher in the antibody-treated animals and administration of the antibodies 30 min after injury was as effective as preburn administration in preserving blood flow. At 72 hr post-burn all antibody-treated animals had blood flow in the areas at risk for progression (i.e., the zone of stasis) at or above baseline levels while the control animals had levels equal to 34.7 ± 12% of baseline ( P < 0.05 by analysis of variance and Mann-Whitney U test). These results suggest that PMNs play an important role in the pathogenesis of burn wound progression, and that this progression can be attenuated by modulating PMN-EC adherence.